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Protectin DX ameliorates palmitate- or high-fat diet-induced insulin resistance and inflammation through an AMPK-PPARα-dependent pathway in mice.
Sci Rep 2017; 7(1):1397SR

Abstract

Protectin DX (PDX), a double lipoxygenase derivative of docosahexaenoic acid, has been reported to attenuate inflammation and insulin resistance. In the current study, we explored the effects of PDX on hyperlipidemia-induced insulin resistance and inflammation through AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor α (PPARα). PDX attenuated the impairment of insulin receptor substrate 1/Akt-mediated insulin signaling in palmitate-treated differentiated C2C12 cells and soleus skeletal muscle of HFD-fed mice. Furthermore, PDX treatment significantly ameliorated HFD-induced weight gain and improved glucose tolerance in mice. Nuclear factor kB nuclear translocation, inhibitory kBα phosphorylation, and expression of proinflammatory cytokines were markedly attenuated by PDX in both in vitro and in vivo models. PDX treatment markedly augmented AMPK phosphorylation and PPARα expression in C2C12 cells and in skeletal muscle of mice. AMPK- and PPARα-specific siRNAs significantly abrogated the suppressive effects of PDX on palmitate-induced insulin resistance and inflammation. Furthermore, PDX markedly stimulated the expression of genes related to fatty acid oxidation. These effects of PDX were significantly suppressed by AMPK and PPARα siRNAs. In conclusion, our results demonstrate that PDX ameliorates insulin resistance and inflammation and stimulates fatty acid oxidation through AMPK- and PPARα-mediated pathways in skeletal muscle.

Authors+Show Affiliations

Research Administration Team, Seoul National University Bundang Hospital, Gyeonggi, Republic of Korea.Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, Republic of Korea.Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea. Faculty of Veterinary Medicine, Cairo University, 12211, Giza, Egypt.Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea. jhjeong3@cau.ac.kr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28469249

Citation

Jung, Tae Woo, et al. "Protectin DX Ameliorates Palmitate- or High-fat Diet-induced Insulin Resistance and Inflammation Through an AMPK-PPARα-dependent Pathway in Mice." Scientific Reports, vol. 7, no. 1, 2017, p. 1397.
Jung TW, Kim HC, Abd El-Aty AM, et al. Protectin DX ameliorates palmitate- or high-fat diet-induced insulin resistance and inflammation through an AMPK-PPARα-dependent pathway in mice. Sci Rep. 2017;7(1):1397.
Jung, T. W., Kim, H. C., Abd El-Aty, A. M., & Jeong, J. H. (2017). Protectin DX ameliorates palmitate- or high-fat diet-induced insulin resistance and inflammation through an AMPK-PPARα-dependent pathway in mice. Scientific Reports, 7(1), p. 1397. doi:10.1038/s41598-017-01603-9.
Jung TW, et al. Protectin DX Ameliorates Palmitate- or High-fat Diet-induced Insulin Resistance and Inflammation Through an AMPK-PPARα-dependent Pathway in Mice. Sci Rep. 2017 05 3;7(1):1397. PubMed PMID: 28469249.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protectin DX ameliorates palmitate- or high-fat diet-induced insulin resistance and inflammation through an AMPK-PPARα-dependent pathway in mice. AU - Jung,Tae Woo, AU - Kim,Hyoung-Chun, AU - Abd El-Aty,A M, AU - Jeong,Ji Hoon, Y1 - 2017/05/03/ PY - 2017/01/09/received PY - 2017/04/04/accepted PY - 2017/5/5/entrez PY - 2017/5/5/pubmed PY - 2018/9/13/medline SP - 1397 EP - 1397 JF - Scientific reports JO - Sci Rep VL - 7 IS - 1 N2 - Protectin DX (PDX), a double lipoxygenase derivative of docosahexaenoic acid, has been reported to attenuate inflammation and insulin resistance. In the current study, we explored the effects of PDX on hyperlipidemia-induced insulin resistance and inflammation through AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor α (PPARα). PDX attenuated the impairment of insulin receptor substrate 1/Akt-mediated insulin signaling in palmitate-treated differentiated C2C12 cells and soleus skeletal muscle of HFD-fed mice. Furthermore, PDX treatment significantly ameliorated HFD-induced weight gain and improved glucose tolerance in mice. Nuclear factor kB nuclear translocation, inhibitory kBα phosphorylation, and expression of proinflammatory cytokines were markedly attenuated by PDX in both in vitro and in vivo models. PDX treatment markedly augmented AMPK phosphorylation and PPARα expression in C2C12 cells and in skeletal muscle of mice. AMPK- and PPARα-specific siRNAs significantly abrogated the suppressive effects of PDX on palmitate-induced insulin resistance and inflammation. Furthermore, PDX markedly stimulated the expression of genes related to fatty acid oxidation. These effects of PDX were significantly suppressed by AMPK and PPARα siRNAs. In conclusion, our results demonstrate that PDX ameliorates insulin resistance and inflammation and stimulates fatty acid oxidation through AMPK- and PPARα-mediated pathways in skeletal muscle. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/28469249/Protectin_DX_ameliorates_palmitate__or_high_fat_diet_induced_insulin_resistance_and_inflammation_through_an_AMPK_PPARα_dependent_pathway_in_mice_ L2 - http://dx.doi.org/10.1038/s41598-017-01603-9 DB - PRIME DP - Unbound Medicine ER -